1. Technical Field
Aspects of the disclosed subject matter are generally related to methods and compositions for reducing or inhibiting aggregate formation, in particular intracellular aggregate formation mediated by p62.
2. Related Art
Neurodegeneration is a broad pathology of the nervous system and is found in diseases such as Alzheimer's disease (AD), Parkinson's disease, ALS, head trauma, epilepsy and stroke. As many as 4.5 million Americans are believed to suffer from AD alone. The specific cause of neurodegeneration in any particular disease or disorder often remains a mystery; however, research is beginning to reveal a common theme among neurodegenerative diseases. It appears that disorders of protein shape or protein accumulation may contribute to neurodegeneration. Indeed, many neurodegenerative diseases including AD are characterized by ubiquitin-positive proteinaceous aggregates or inclusion bodies.
Although neurodegenerative diseases affect a large number of individuals, there are few therapies available to treat or prevent these disorders. Some existing therapies include, for example, the transplantation of stem cells into areas of the brain. The heterologous transplantation of stem cells obtained from a source other than the patient presents both ethical and practical problems. The transplantation of embryonic stem cells is ethically controversial because the stem cells are obtained from embryos. Moreover, it is unclear whether such transplanted cells can survive in the patient over the long term and successfully ameliorate or prevent neurodegeneration. With the discovery of neural stem cells or adult stem cells, the possibility of autogolous transplantation has become possible. However, these neural or adult stem cells must be located, successfully cultivated, and induced to differentiate into the needed cells or tissue.
Other therapies include the use of small molecules. One small molecule therapy includes the administration of dopamine to treat patients suffering with Parkinson's Disease; however, dopamine treats symptoms of Parkinson's Disease, for example tremors. Dopamine does not appear to treat the underlying cause of Parkinson's Disease, nor does it appear to prevent the progression of the disease. In addition, the therapeutic effects of dopamine begin to wear-off in increasingly shorter times the longer a patient has been on the drug.
Thus, there is a need for methods and compositions for treating neurological pathologies and for identifying additional compositions for the treatment of neurological pathologies.